A common A/G single nucleotide polymorphism (A870G) in exon 4 of the cyclin D1 gene, CCND1, is associated with the presence of 2 distinct mRNA transcripts for this G1/S regulatory protein, and CCND1 genotype has been related to prognosis in lung cancer and head and neck carcinoma.
As expected, small interfering RNAs that reduced UBP43 expression also decreased cyclin D1 levels and increased apoptosis in a panel of lung cancer cell lines.
At the overall analysis the CCND1 870A allele appeared to be associated with elevated lung cancer risk (for allele model, pooled OR=1.24, 95% CI: 1.08-1.44, P=0.004; for homozygous model, pooled OR=1.45, 95% CI: 1.14-1.84, P=0.003; for recessive model, pooled OR=1.29, 95% CI: 1.06-1.58, P=0.013; for dominant model, pooled OR=1.33, 95% CI: 1.08-1.65, P=0.009).
Comparative modeling and docking studies of p16ink4/cyclin D1/Rb pathway genes in lung cancer revealed functionally interactive residue of RB1 and its functional partner E2F1.
Compared with homozygous wild-types, the homozygous variant genotypes of STK15 F31I and CCND1G870A were associated with a significantly altered lung cancer risk with ORs of 0.58 (95% CI, 0.37-0.90) and 1.26 (95% CI, 1.03-1.53), respectively.
Functional studies demonstrated that the 13H3 antibody suppressed lung cancer cell lines ANIP-973 and A549 proliferation in vitro and inhibit ANIP973 xenograft tumors growth in vivo by inducing cell-cycle arrest at G1 phase, with up-regulation of p27 and down-regulation of cyclin D1.
Here we demonstrate that diazoxide inhibited the proliferation of lung cancer cells as well as the transcription of cell cycle-related protein Cyclin D1.
Histone deacetylases (HDACs) inhibitor is a promising new approach to the treatment of lung cancer therapy via inhibiting cell growth and inducing apoptosis. miR-15a and miR-16-1 are important tumor suppressors through modulating B cell lymphoma 2 (Bcl-2), Cyclin D1, D2, and others.
In accordance with the developmental mode of lung cancer established by Sekine et al., we assumed that the occurrence and development of lung cancer were linked not only to gene loss in the 3p region (WNT7A, 3p25) and genetic mutations in the 9p region but also to similar events in the regions of 1p36.2 (FRAP1), 6q25.2-q27 (PARK2), and 11q13 (CCND1).
In conclusion, it is suggested that the CCND1 G/A polymorphism is associated with the early onset of lung cancer in men and contributes to susceptibility to lung cancer, especially squamous cell cancer, in this population.
In conclusion, Rsf-1 is overexpressed in NSCLC and contributes to malignant cell growth by cyclin D1 and ERK modulation, which makes Rsf-1 a candidate therapeutic target in lung cancer.